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Author Eleftheria Letsiou

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Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

Holger Müller-Redetzky, Ute Kellermann, Sandra-Maria Wienhold, Birgitt Gutbier, Jasmin Lienau, Katharina Hellwig, Katrin Reppe, Eleftheria Letsiou, Thomas Tschernig, Markus Scholz, Peter Ahnert, Christian Maasch, Kai Hoehlig, Sven Klussmann, Axel Vater, Theresa C Firsching, Judith Hoppe, Norbert Suttorp, Martin Witzenrath,

BACKGROUND:Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions. The authors hypothesized that C5a ... Read more >>

Anesthesiology (Anesthesiology)
[2020, 132(4):795-807]

Cited: 0 times

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Arg mediates LPS-induced disruption of the pulmonary endothelial barrier.

Alicia N Rizzo, Patrick Belvitch, Regaina Demeritte, Joe G N Garcia, Eleftheria Letsiou, Steven M Dudek,

Acute Respiratory Distress Syndrome (ARDS) is a devastating disease process that involves dysregulated inflammation and decreased alveolar-capillary barrier function. Despite increased understanding of the pathophysiology, no effective targeted therapies exist to treat ARDS. Recent preclinical studies suggest that the multi-tyrosine kinase inhibitor, imatinib, which targets the Abl kinases c-Abl and ... Read more >>

Vascul. Pharmacol. (Vascular pharmacology)
[2020, 128-129:106677]

Cited: 0 times

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Degradation of group V secretory phospholipase A2 in lung endothelium is mediated by autophagy.

Lucille N Meliton, Xiangdong Zhu, Mary Brown, Yulia Epshtein, Takeshi Kawasaki, Eleftheria Letsiou, Steven M Dudek,

Group V secretory phospholipase A2 (gVPLA2) is a potent inflammatory mediator in mammalian tissues that hydrolyzes phospholipids and initiates eicosanoid biosynthesis. Previous work has demonstrated that multiple inflammatory stimuli induce its expression and secretion in several cell types, including the lung endothelium. However, little is known about the mechanism(s) by ... Read more >>

Microvasc. Res. (Microvascular research)
[2020, 129:103954]

Cited: 0 times

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Sphingosine Kinase 1 Regulates Inflammation and Contributes to Acute Lung Injury in Pneumococcal Pneumonia via the Sphingosine-1-Phosphate Receptor 2.

Birgitt Gutbier, Stefanie M Schönrock, Carolin Ehrler, Rainer Haberberger, Kristina Dietert, Achim D Gruber, Wolfgang Kummer, Laura Michalick, Wolfgang M Kuebler, Andreas C Hocke, Kolja Szymanski, Eleftheria Letsiou, Anja Lüth, Fabian Schumacher, Burkhard Kleuser, Timothy J Mitchell, Wilhelm Bertrams, Bernd Schmeck, Denise Treue, Frederick Klauschen, Torsten T Bauer, Mario Tönnies, Norbert Weissmann, Stefan Hippenstiel, Norbert Suttorp, Martin Witzenrath, ,

OBJECTIVES:Severe pneumonia may evoke acute lung injury, and sphingosine-1-phosphate is involved in the regulation of vascular permeability and immune responses. However, the role of sphingosine-1-phosphate and the sphingosine-1-phosphate producing sphingosine kinase 1 in pneumonia remains elusive. We examined the role of the sphingosine-1-phosphate system in regulating pulmonary vascular barrier function ... Read more >>

Crit. Care Med. (Critical care medicine)
[2018, 46(3):e258-e267]

Cited: 2 times

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Pneumolysin induced mitochondrial dysfunction leads to release of mitochondrial DNA.

Andreas Nerlich, Maren Mieth, Eleftheria Letsiou, Diana Fatykhova, Katja Zscheppang, Aki Imai-Matsushima, Thomas F Meyer, Lisa Paasch, Timothy J Mitchell, Mario Tönnies, Torsten T Bauer, Paul Schneider, Jens Neudecker, Jens C Rückert, Stephan Eggeling, Maria Schimek, Martin Witzenrath, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke,

Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):182]

Cited: 6 times

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The ARP 2/3 complex mediates endothelial barrier function and recovery.

Patrick Belvitch, Mary E Brown, Brittany N Brinley, Eleftheria Letsiou, Alicia N Rizzo, Joe G N Garcia, Steven M Dudek,

Pulmonary endothelial cell (EC) barrier dysfunction and recovery is critical to the pathophysiology of acute respiratory distress syndrome. Cytoskeletal and subsequent cell membrane dynamics play a key mechanistic role in determination of EC barrier integrity. Here, we characterizAQe the actin related protein 2/3 (Arp 2/3) complex, a regulator of peripheral ... Read more >>

Pulm Circ (Pulmonary circulation)
[2017, 7(1):200-210]

Cited: 4 times

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Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.

Sergei M Danilov, Heinrich Lünsdorf, Henry T Akinbi, Andrew B Nesterovitch, Yuliya Epshtein, Eleftheria Letsiou, Olga V Kryukova, Tobias Piegeler, Elena Z Golukhova, David E Schwartz, Randal O Dull, Richard D Minshall, Olga A Kost, Joe G N Garcia,

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process ... Read more >>

Sci Rep (Scientific reports)
[2016, 6:34913]

Cited: 6 times

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Parkin regulates lipopolysaccharide-induced proinflammatory responses in acute lung injury.

Eleftheria Letsiou, Saad Sammani, Huashan Wang, Patrick Belvitch, Steven M Dudek,

The acute respiratory distress syndrome (ARDS) is a serious condition resulting from direct or indirect lung injury that is associated with high mortality and morbidity. A key biological event in the pathogenesis of the acute lung injury (ALI) that causes acute respiratory distress syndrome is activation of the lung endothelium ... Read more >>

Transl Res (Translational research : the journal of laboratory and clinical medicine)
[2017, 181:71-82]

Cited: 6 times

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Imatinib attenuates inflammation and vascular leak in a clinically relevant two-hit model of acute lung injury.

Alicia N Rizzo, Saad Sammani, Adilene E Esquinca, Jeffrey R Jacobson, Joe G N Garcia, Eleftheria Letsiou, Steven M Dudek,

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), an illness characterized by life-threatening vascular leak, is a significant cause of morbidity and mortality in critically ill patients. Recent preclinical studies and clinical observations have suggested a potential role for the chemotherapeutic agent imatinib in restoring vascular integrity. Our prior work demonstrates ... Read more >>

Am. J. Physiol. Lung Cell Mol. Physiol. (American journal of physiology. Lung cellular and molecular physiology)
[2015, 309(11):L1294-304]

Cited: 14 times

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Unique Toll-Like Receptor 4 Activation by NAMPT/PBEF Induces NFκB Signaling and Inflammatory Lung Injury.

Sara M Camp, Ermelinda Ceco, Carrie L Evenoski, Sergei M Danilov, Tong Zhou, Eddie T Chiang, Liliana Moreno-Vinasco, Brandon Mapes, Jieling Zhao, Gamze Gursoy, Mary E Brown, Djanybek M Adyshev, Shahid S Siddiqui, Hector Quijada, Saad Sammani, Eleftheria Letsiou, Laleh Saadat, Mohammed Yousef, Ting Wang, Jie Liang, Joe G N Garcia,

Ventilator-induced inflammatory lung injury (VILI) is mechanistically linked to increased NAMPT transcription and circulating levels of nicotinamide phosphoribosyl-transferase (NAMPT/PBEF). Although VILI severity is attenuated by reduced NAMPT/PBEF bioavailability, the precise contribution of NAMPT/PBEF and excessive mechanical stress to VILI pathobiology is unknown. We now report that NAMPT/PBEF induces lung NFκB ... Read more >>

Sci Rep (Scientific reports)
[2015, 5:13135]

Cited: 24 times

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Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in murine models of inflammatory lung injury.

Liliana Moreno-Vinasco, Hector Quijada, Saad Sammani, Jessica Siegler, Eleftheria Letsiou, Ryan Deaton, Laleh Saadat, Rafe S Zaidi, Joe Messana, Peter H Gann, Roberto F Machado, Wenli Ma, Sara M Camp, Ting Wang, Joe G N Garcia,

We previously identified the intracellular nicotinamide phosphoribosyltransferase (iNAMPT, aka pre-B-cell colony enhancing factor) as a candidate gene promoting acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) with circulating nicotinamide phosphoribosyltransferase potently inducing NF-κB signaling in lung endothelium. iNAMPT also synthesizes intracellular nicotinamide adenine dinucleotide (iNAD) in response to ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2014, 51(2):223-228]

Cited: 9 times

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Pleiotropic effects of interleukin-6 in a "two-hit" murine model of acute respiratory distress syndrome.

Julia L Goldman, Saad Sammani, Carrie Kempf, Laleh Saadat, Eleftheria Letsiou, Ting Wang, Liliana Moreno-Vinasco, Alicia N Rizzo, Jeffrey D Fortman, Joe G N Garcia,

Patients with acute respiratory distress syndrome (ARDS) exhibit elevated levels of interleukin-6 (IL-6), which correlate with increased morbidity and mortality. The exact role of IL-6 in ARDS has proven difficult to study because it exhibits either pro- or anti-inflammatory actions in mouse models of lung injury, depending on the model ... Read more >>

Pulm Circ (Pulmonary circulation)
[2014, 4(2):280-288]

Cited: 21 times

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FTY720 (s)-phosphonate preserves sphingosine 1-phosphate receptor 1 expression and exhibits superior barrier protection to FTY720 in acute lung injury.

Lichun Wang, Saad Sammani, Liliana Moreno-Vinasco, Eleftheria Letsiou, Ting Wang, Sara M Camp, Robert Bittman, Joe G N Garcia, Steven M Dudek,

Effective therapies are needed to reverse the increased vascular permeability that characterizes acute inflammatory diseases such as acute lung injury. FTY720 is a pharmaceutical analog of the potent barrier-enhancing phospholipid, sphingosine 1-phosphate. Because both FTY720 and sphingosine 1-phosphate have properties that may limit their usefulness in patients with acute lung ... Read more >>

Crit. Care Med. (Critical care medicine)
[2014, 42(3):e189-99]

Cited: 19 times

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Endothelial protein C receptor polymorphisms and risk of severe sepsis in critically ill patients.

Alice G Vassiliou, Nikolaos A Maniatis, Anastasia Kotanidou, Marina Kallergi, Foteini S Karystinaki, Eleftheria Letsiou, Constantinos Glynos, Petros Kopterides, Dimitra Vassiliadi, Nikitas Nikitas, Ioanna Dimopoulou, Apostolos Armaganidis, Stylianos E Orfanos,

PURPOSE:Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients. METHODS:Three polymorphisms ... Read more >>

Intensive Care Med (Intensive Care Medicine)
[2013, 39(10):1752-1759]

Cited: 5 times

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Role of caveolin-1 expression in the pathogenesis of pulmonary edema in ventilator-induced lung injury.

Nikolaos A Maniatis, Matina Kardara, Dan Hecimovich, Eleftheria Letsiou, Maricela Castellon, Charalambos Roussos, Vasily Shinin, E Gina Votta-Vellis, David E Schwartz, Richard D Minshall,

Caveolin-1 is a key regulator of pulmonary endothelial barrier function. Here, we tested the hypothesis that caveolin-1 expression is required for ventilator-induced lung injury (VILI). Caveolin-1 gene-disrupted (Cav-1(-/-)) and age-, sex-, and strain-matched wild-type (WT) control mice were ventilated using two protocols: volume-controlled with protective (8 mL/kg) versus injurious (21 ... Read more >>

Pulm Circ (Pulmonary circulation)
[2012, 2(4):452-460]

Cited: 17 times

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Sphingosine-1-phosphate receptor-3 is a novel biomarker in acute lung injury.

Xiaoguang Sun, Patrick A Singleton, Eleftheria Letsiou, Jing Zhao, Patrick Belvitch, Saad Sammani, Eddie T Chiang, Liliana Moreno-Vinasco, Michael S Wade, Tong Zhou, Bin Liu, Ioannis Parastatidis, Leonor Thomson, Harry Ischiropoulos, Viswanathan Natarajan, Jeffrey R Jacobson, Roberto F Machado, Steven M Dudek, Joe G N Garcia,

The inflamed lung exhibits oxidative and nitrative modifications of multiple target proteins, potentially reflecting disease severity and progression. We identified sphingosine-1-phosphate receptor-3 (S1PR3), a critical signaling molecule mediating cell proliferation and vascular permeability, as a nitrated plasma protein in mice with acute lung injury (ALI). We explored S1PR3 as a ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2012, 47(5):628-636]

Cited: 29 times

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Type 2 deiodinase and host responses of sepsis and acute lung injury.

Shwu-Fan Ma, Lishi Xie, Maria Pino-Yanes, Saad Sammani, Michael S Wade, Eleftheria Letsiou, Jessica Siegler, Ting Wang, Giovanni Infusino, Rick A Kittles, Carlos Flores, Tong Zhou, Bellur S Prabhakar, Liliana Moreno-Vinasco, Jesus Villar, Jeffrey R Jacobson, Steven M Dudek, Joe G N Garcia,

The role of thyroid hormone metabolism in clinical outcomes of the critically ill remains unclear. Using preclinical models of acute lung injury (ALI), we assessed the gene and protein expression of type 2 deiodinase (DIO2), a key driver for synthesis of biologically active triiodothyronine, and addressed potential association of DIO2 ... Read more >>

Am. J. Respir. Cell Mol. Biol. (American journal of respiratory cell and molecular biology)
[2011, 45(6):1203-1211]

Cited: 26 times

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Mild stretch activates cPLA2 in alveolar type II epithelial cells independently through the MEK/ERK and PI3K pathways.

Eleftheria Letsiou, Ei Kitsiouli, George Nakos, Marilena E Lekka,

Alveolar epithelial type II cells (AT II) in which lung surfactant synthesis and secretion take place, are subjected to low magnitude stretch during normal breathing. The aim of the study was to explore the effect of mild stretch on phospholipase A(2) (PLA(2)) activation, an enzyme known to be involved in ... Read more >>

Biochim. Biophys. Acta (Biochimica et biophysica acta)
[2011, 1811(6):370-376]

Cited: 6 times

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Inhaled activated protein C protects mice from ventilator-induced lung injury.

Nikolaos A Maniatis, Eleftheria Letsiou, Stylianos E Orfanos, Matina Kardara, Ioanna Dimopoulou, Georgios Nakos, Marilena E Lekka, Charalambos Roussos, Apostolos Armaganidis, Anastasia Kotanidou,

INTRODUCTION: Activated Protein C (APC), an endogenous anticoagulant, improves tissue microperfusion and endothelial cell survival in systemic inflammatory states such as sepsis, but intravenous administration may cause severe bleeding. We have thus addressed the role of APC delivered locally by inhalation in preventing acute lung injury from alveolar overdistention and ... Read more >>

Crit Care (Critical care (London, England))
[2010, 14(2):R70]

Cited: 20 times

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